GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy.2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group.4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of AIN-93 diet on mortality and cardiac remodeling after myocardial infarction in rats

Background: The AIN-93 diet was proposed by the American Institute of Nutrition with the objective of standardising studies in experimental nutrition. Our objective was to analyze the effects of AIN-93 diet after myocardial infarction in rats.Methods: Post weaning, the animals were divided into two groups: control (C, n=62), fed the standard diet of our laboratory (Labina); AIN-93 Group (n=70), fed the AIN-93 diet. Achieving 250 g, the animals were subjected to myocardial infarction.Results: Early mortality was increased in AIN-93 animals, associated with lower serum levels of calcium, magnesium, potassium, sodium, and phosphorus. on the other hand, after 90 days, AIN-93 showed smaller normalized left ventricular dimensions. The caloric and carbohydrate intake was smaller, but the fat intake was higher in AIN-93 rats. AIN-93 group also showed increased levels of beta-hydroxyacylcoenzyme A dehydrogenase and citrate synthase. In addition, serum levels of insulin and cardiac levels of malondialdehyde, metalloproteinases-2 and -9, and TNF-alpha and IFN-gamma were decreased in the AIN-93 group.Conclusion: AIN-93 diet increased early mortality, while attenuated the chronic remodeling process after experimental coronary occlusion. Therefore, this diet has biological effects and should be use with attention in this model. (C) 2010 Elsevier B.V. All rights reserved.

Alcoholism and alcohol abstinence: N-acetylcysteine to improve energy expenditure, myocardial oxidative stress, and energy metabolism in alcoholic heart disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Annexin 1 peptides protect against experimental myocardial ischemia-reperfusion: analysis of their mechanism of action

Myocardial reperfusion injury is associated with the infiltration of blood-borne polymorphonuclear leukocytes. We have previous described the protection afforded by annexin 1 (ANXA1) in an experimental model of rat myocardial ischemia-reperfusion (IR) injury. We examined the 1) amino acid region of ANXA1 that retained the protective effect in a model of rat heart IR; 2) changes in endogenous ANXA1 in relation to the IR induced damage and after pharmacological modulation; and 3) potential involvement of the formyl peptide receptor (FPR) in the protective action displayed by ANXA1 peptides. Administration of peptide Ac2-26 at 0, 30, and 60 min postreperfusion produced a significant protection against IR injury, and this was associated with reduced myeloperoxidase activity and IL-1 beta levels in the infarcted heart. Western blotting and electron microscopy analyses showed that IR heart had increased ANXA1 expression in the injured tissue, associated mainly with the infiltrated leukocytes. Finally, an antagonist to the FPR receptor selectively inhibited the protective action of peptide ANXA1 and its derived peptides against IR injury. Altogether, these data provide further insight into the protective effect of ANXA1 and its mimetics and a rationale for a clinical use for drugs developed from this line of research.

Maximum entropy, fractal dimension and lacunarity in quantification of cellular rejection in myocardial biopsy of patients submitted to heart transplantation

This paper presents a method for the quantification of cellular rejection in endomyocardial biopsies of patients submitted to heart transplant. The model is based on automatic multilevel thresholding, which employs histogram quantification techniques, histogram slope percentage analysis and the calculation of maximum entropy. The structures were quantified with the aid of the multi-scale fractal dimension and lacunarity for the identification of behavior patterns in myocardial cellular rejection in order to determine the most adequate treatment for each case.

Myocardial protection by continuous, blood, antegrade-retrograde cardioplegia in rabbits

OBJETIVO: Estudar a eficácia e a segurança da cardioplegia sanguínea, aterógrada-retrógrada contínua, por meio da avaliação da função ventricular. MÉTODOS: Os coelhos foram divididos em quatro grupos: Controle-C(n=10); isquêmico e cardioplegia cristaloide-IC(n=10; isquêmico e cardioplegia sanguínea-IB(n=10; isquêmico sem cardioplegia-INC(n=10. Após o período isquêmico do protocolo a função ventricular foi analisada pela técnica do balão intra-ventricular. RESULTADOS: a pressão desenvolvida intra-ventricular (IVDP) foi: C(92,90± 6,86mmHg); IC(77,78± 6,15mmHg); IB(93,64 ±5,09mmHg); INC(39,46 ±8,91mmHg) p<0,005. a primeira derivada temporal da pressão ventricular na sua deflexão positiva: C(1137,50± 92,23mmHg/sec); IC(1130,62 ±43,78mmHg/sec); IB(1187,58± 88,38mmHg/sec); INC(620,02± 43,80mmHg/se) p<0,005. A primeira derivada da pressão ventricular na sua deflexão negativa: C(770,00± 73,41mmHg/sec); IC(610,03 ±47,43mmg/sec); IB(762,53 ±46,02mmHg/sec); INC(412,35 ±84,36mmHg/sec) p<0,005. A relação do coeficiente angular logarítmico foi: C(0,108± 0,02); IC(0,159± 0,038); IB(0,114 ±0,016); INC(0,175± 0,038) p<0,05. CONCLUSÃO: No modelo experimental estudado o grupo isquêmico protegido pela cardioplegia sanguínea apresentou melhor função ventricular que os grupos protegidos por cardioplegia cristalóide e não protegido.

FUNCTIONAL AND ULTRASTRUCTURAL EVALUATION OF MYOCARDIAL PROTECTION PROVIDED BY INTERMITTENT CORONARY SINUS PERFUSION IN THE ISOLATED DOG HEART

1. The protection offered by intermittent perfusion of of cardioplegic solution through the coronary sinus was investigated in isovolumic blood-perfused dog heart preparations submitted to 60 min of ischemia and 45 min of reperfusion.2. The preparations were divided into three treatment groups: a) coronary sinus, consisting of preparations (N = 10) perfused through the coronary sinus under 40 cm water pressure; b) aortic, consisting of preparations (N = 10) perfused through the aortic stump under 100 mmHg pressure; c) control, consisting of hearts (N = 9) that were not perfused with cardioplegic solution.3. Properties of contractile capacity and relaxation were markedly impaired in the control group but were preserved to a comparable extent in the groups perfused with cardioplegic solution through the aorta and coronary sinus. Developed pressure decreased in the control group (before ischemia: 70 +/- 5.5 mmHg; after reperfusion: 35 +/- 12 mmHg; P < 0.05) and didn't vary in the aortic group (from 69 +/- 4 mmHg to 65 +/- 13 mmHg; P > 0.05) and coronary sinus group (from 69 +/- 4.6 mmHg to 60 +/- 10 mmHg; P > 0.05). Myocardial relaxation was evaluated by the +/- dp/dt ratio. In the control group there was impairment of myocardial relaxation as indicated by an increase of this index after reperfusion (from 1.05 +/- 0.05 to 1.46 +/- 0.23; P < 0.05), whereas in the aortic (from 1.10 +/- 0.13 to 1.15 +/- 0.20; P > 0.05) and the coronary sinus (from 1.03 +/- 0.14 to 1.08 +/- 0.16; P > 0.05) groups there was no variation. Ultrastructural changes in the myocardium were negligible in all three groups at the end of reperfusion.4. We conclude that intermittent perfusion of a hypothermic cardioplegic solution through the coronary sinus is effective for the protection of the myocardium during total ischemia.

Ventricular remodeling and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

The effects of protein-calorie malnutrition (PCM) on heart structure and function are not completely understood. We studied heart morphometric, functional, and biochemical characteristics in undernourished young Wistar rats. They were submitted to PCM from birth (undernourished group, UG). After 10 wk, left ventricle function was studied using a Langendorff preparation. The results were compared with age-matched rats fed ad libitum (control group, CG). The UG rats achieved 47% of the body weight and 44% of the left ventricular weight (LVW) of the CG. LVW-to-ventricular volume ratio was smaller and myocardial hydroxyproline concentration was higher in the UG. Left ventricular systolic function was not affected by the PCM protocol. The myocardial stiffness constant was greater in the UG, whereas the end-diastolic pressure-volume relationship was not altered. In conclusion, the heart is not spared from the adverse effects of PCM. There is a geometric alteration in the left ventricle with preserved ventricular compliance despite the increased passive myocardial stiffness. The systolic function is preserved.